DESCRIPTION: (Applicant's Description) The long-term objective is the development of innovative approaches at the Moffitt Cancer Center to improve the and quality of life of adult with primary malignant tumors of the central nervous system (CNS) - by the initiation, co analysis, and reporting of Phase I/II clinical trials focused on promising molecular biologic strategies within the organizational framework of the NABTT, "New Approaches to Brain Tumor Therapy", CNS cancer consortium. A major research thrust at the Moffit" Cancer Center is in place, in three areas l i nked to neuro-oncology, to develop technologies and discover novel cytostatic and cytotoxic agents suitable for Phase I/II clinical testing: 1) Drug Discovery, evaluating i) antagonists of angiogenesis and invasiveness; ii) inhibitors of ras-mediated signal transduction pathways, eg., farnesyl transferase; iii) topoisomerase inhibitors, and iv) inhibitors of multidrug resistance; 2) Neuro-imaging, developing MRI technology for therapeutic trials in neuro-oncology; and 3) Genetic and Immunological Therapies, inhibition of t u m o r growth using immune modulators and antibody-based approaches. Specifically, the Brain Tumor Research Laboratory will continue to develop angiogenesis inhibitors: two Phase II protocols using penicillamine for malignant gliomas are under review at the NABTT Central Office. Candidate molecules for Phase I/II protocols include i) angiogenesis antagonists: captopril, platelet- factor four and inhibitors of urokinase plasminogen activator; ii) signal transduction Inhibitors; iii) a benzamide-derivative chemosensitizer to counter multiple drug resistance; iv) cytokines (eg., IL-12), and v) targeted antibodies. The Neurooncology Program at the Moffitt Cancer Center will build on its track record of patient accrual, transnational research, protocol development, and provide the CNS Consortium: (1) 20 to 30 patients per year with primary brain tumors; (2) an expert multidisciplinary clinical team; (3) extensive clinical and laboratory resources for Interactive collaborations with other NABTT centers; (4) grant-supported brain tumor biology and pharmacology research, including a NCI-sponsored National Cooperative Drug Discovery Group; (5) expertise in oncology, pharmacology, new drug development, Phase I and II c l i nical trials; (6) state-of-the-art radiation therapy; stereotactic radiosurgery; - computer-driven, navigational neurosurgery; and advanced MR neuroimaging; (7) expertise in biostatistics, protocol development, data management, and the coordination of multi-institutional studies; (8) an established Brain Tumor Bank with correlative studies of glioma biomarkers; and (9) Phase II protocols submitted to NABTT Central Office for anti-angiogenesis and other novel approaches to brain tumors.